SYNTHESIS OF CLAVULACTONE--A POTENTIAL ANTITUMOR AGENT

本研究方案的具体目的是开发一种高效、对映选择性的合成克拉维内酯的方法。克来拉内酯是从一种未知的克氏杆菌中分离得到的，属于海洋二萜中的多拉贝烷类化合物。这些二萜类化合物含有特征的反式双环[9.3.0]十四烷骨架。建议的合成包括使用立体专一性的三组分偶联过程形成骨架，然后形成四取代硅烯醇醚，然后是Lewis酸催化的碳环闭合。克拉维拉通对Ehrlich腹水癌(EAC)细胞具有细胞毒作用，IC50为8µg/mL，是一种潜在的抗肿瘤药物。有效的合成将使类似物的制备和生物学评价以及与结构相关的天然产物得以实现。

The specify aim of this research proposal is to develop an efficient and enantioselective approach for the synthesis of clavulactone. Clavulactone was isolated from an unidentified species of Clavularia and belong to the dolabellane class of marine diterpenoids. These diterpenoids contain characteristic trans-bicyclo [9.3.0] tetradecane skeletons. The proposed synthesis involves formation of the skeleton using a stereospecific three component coupling process for the formation of tetrasubstituted silyl enol ethers followed by Lewis acid catalysed carbocyclic ring closure. Clavulactone exhibits cytotoxicity against Ehrlich ascites carcinoma (EAC) cells, IC50 8 mug/mL, which makes it a potential lead for an anti- tumor agent. An efficient synthesis would allow for the preparation and biological evaluation of analogues as well as structurally related natural products.